This program project aims to discover the biological bases of and environmental influences on the social communication deficits in autism. The first two projects propose experimental interventions and longitudinal follow-ups to test the extent to which joint attention, symbolic play, and language can be modified. Based on results showing that particular caregiver behaviors lead to gains in language skills over a 15-year period of development, Project I will test an experimental approach to modifying caregiver behaviors and measuring the consequences. Project II will follow a group of children whose nonverbal communication and play skills were improved through intervention, and will also attempt to generalize the intervention from skilled clinicians to paraprofessionals with a new sample of children. In order to understand the basis for the deficits associated with autism, Project III aims to explicate the role that duplication of chromosome 15q plays in autism by assessing the phenotypic sequelae in probands with known duplications. The proposed project also plans to define the autism critical region by detailed examination of rearrangements in probands with unusual breakpoints or imprinting errors. Lastly, the extent of cryptic duplication in the population of idiopathic autism will be investigated with newly developed mapping techniques. Project IV focuses on the neuroanatomical bases of social communication deficits in autism. The proposed project will use fMRI to investigate fundamental aspects of information processing: imitation, joint attention, and referencing. These studies will test the hypothesis that deficits in the response properties of specific neural populations, such as mirror neurons, and deficits in the brain's reward systems underlie impairments in perception of referencing and joint attention, which give rise to the social communication deficits in autism.